Obstetric Anesthesia Workforce Survey: A 30-Year Update.

BACKGROUND: Obstetric Anesthesia Workforce Surveys were conducted in 1981, 1992, and 2001, and the 10-year update was conducted in 2012. Anesthesia providers from US hospitals were surveyed to identify the methods used to provide obstetric anesthesia. Our primary hypothesis was that the provision of obstetric anesthesia services has changed in the past 10 years. METHODS: A sample of hospitals was generated based on the number of births per year and US census region. Strata were defined as follows: I ≥ 1500 annual births (n = 341), II ≥ 500 to 1499 annual births (n = 438), and III < 500 annual births (n = 414). Contact email information for the anesthesia provider in charge of obstetric services was obtained by phone call. Electronic questionnaires were sent through email. RESULTS: Administration of neuraxial (referred to as "regional" in previous surveys) labor analgesia was available 24 hours per day in all stratum I hospitals responding to the survey. Respondents across all strata reported high rates of in-house coverage, with 86.3% (95% confidence interval [CI] = 82.7%-90%) of stratum I providers reporting that they provided in-house anesthesiology services for obstetrics. The use of patient-controlled epidural analgesia in stratum I hospitals was reported to be 35% in 2001 and 77.6% (95% CI = 73.2%-82.1%) in this survey. Independent Certified Registered Nurse Anesthetists were reported to provide obstetric anesthesia services in 68% (95% CI = 57.9%-77.0%) of stratum III hospitals. Although 76% (95% CI = 71.2%-80.3%) of responding stratum I hospitals allow postpartum tubal ligations, 14% report inadequate staffing to provide anesthesia either always or at off-hours. CONCLUSIONS: Since 2001, there have been significant changes in how responding hospitals provide obstetric anesthesia care and staff the labor and delivery ward. Obstetric anesthesia surveys, updated every 10 years, continue to provide information about changes in obstetric anesthesia practice.

Psychosocial telephone interventions for patients with cancer and survivors: a systematic review.

OBJECTIVE: Over one third of patients with cancer experience elevated psychosocial distress. As screening for distress becomes more common, the number of patients referred for psychosocial care will increase. Psychosocial telephone interventions are recommended as a convenient and exportable alternative to in-person interventions addressing psychosocial distress. This study reviews the efficacy of randomized controlled trials (RCTs) of psychosocial telephone interventions for patients with cancer. METHODS: We conducted a systematic review of peer-reviewed RCTs evaluating telephone interventions in adult patients with cancer across the survivorship continuum. RESULTS: Through a database search, 480 articles were identified. After manual review, 13 were included, with 7 additional studies identified by back citation, totaling 20 studies. Participants were largely Caucasian, highly educated, with mean age ranging from 49 to 75 years. Most participants were patients with breast cancer (n = 13 studies). Sample sizes were generally small, with most patients recruited from large medical centers. Only one screened for psychosocial need. Interventions varied greatly in length and intensity. Eight studies reported significant effects post-intervention in the hypothesized direction on at least one psychosocial outcome measure. Of these eight studies, four included more than one follow-up assessment; of these, only one reported significant effects at last follow-up. No clear commonalities were found among studies reporting significant effects. CONCLUSIONS: Methodological concerns and lack of consistency in adherence to CONSORT reporting guidelines were identified. This body of research would benefit from well-designed, theory-based RCTs adequately powered to provide more definitive evidence for intervention efficacy. This will probably require multi-institutional collaborations, guided by intervention and research methodology best practices.

Prevalence and predictors of distress in posttreatment adult leukemia and lymphoma survivors.

This paper examines predictors of cancer-specific distress among posttreatment adult leukemia and lymphoma survivors (LLS). Using a survey mailed to LLS in the Colorado Central Cancer Registry (N = 477), the authors developed a multivariable risk profile for distress. Thirty one percent of LLS reported indicators of distress. Significantly higher distress was associated with younger age (p < 0.001) in bivariate analyses. The risk profile included fear of recurrence, financial burden, and younger age. Distress did not attenuate based on time since treatment completion and may persist up to 4 years posttreatment, suggesting a need for intervention, particularly among high-risk LLS.

Early effect of tidal volume on lung injury biomarkers in surgical patients with healthy lungs.

BACKGROUND: The early biological impact of short-term mechanical ventilation on healthy lungs is unknown. The authors aimed to characterize the immediate tidal volume (VT)-related changes on lung injury biomarkers in patients with healthy lungs and low risk of pulmonary complications. METHODS: Twenty-eight healthy patients for knee replacement surgery were prospectively randomized to volume-controlled ventilation with VT 6 (VT6) or 10 (VT10) ml/kg predicted body weight. General anesthesia and other ventilatory parameters (positive end-expiratory pressure, 5 cm H2O, FIO2, 0.5, respiratory rate titrated for normocapnia) were managed similarly in the two groups. Exhaled breath condensate and blood samples were collected for nitrite, nitrate, tumor necrosis factor-α, interleukins-1ß, -6, -8, -10, -11, neutrophil elastase, and Clara Cell protein 16 measurements, at the onset of ventilation and 60 min later. RESULTS: No significant differences in biomarkers were detected between the VT groups at any time. The coefficient of variation of exhaled breath condensate nitrite and nitrate decreased in the VT6 but increased in the VT10 group after 60-min ventilation. Sixty-minute ventilation significantly increased plasma neutrophil elastase levels in the VT6 (35.2 ± 30.4 vs. 56.4 ± 51.7 ng/ml, P = 0.008) and Clara Cell protein 16 levels in the VT10 group (16.4 ± 8.8 vs. 18.7 ± 9.5 ng/ml, P = 0.015). Exhaled breath condensate nitrite correlated with plateau pressure (r = 0.27, P = 0.042) and plasma neutrophil elastase (r = 0.44, P = 0.001). Plasma Clara Cell protein 16 correlated with compliance (r = 0.34, P = 0.014). CONCLUSIONS: No tidal volume-related changes were observed in the selected lung injury biomarkers of patients with healthy lungs after 60-min ventilation. Plasma neutrophil elastase and plasma Clara Cell protein 16 might indicate atelectrauma and lung distention, respectively.

Predictors of early faculty attrition at one Academic Medical Center.

BACKGROUND: Faculty turnover threatens the research, teaching and clinical missions of medical schools. We measured early attrition among newly-hired medical school faculty and identified personal and institutional factors associated with early attrition. METHODS: This retrospective cohort study identified faculty hired during the 2005-2006 academic year at one school. Three-year attrition rates were measured. A 40-question electronic survey measured demographics, career satisfaction, faculty responsibilities, institutional/departmental support, and reasons for resignation. Odds ratios (ORs) and 95 percent confidence intervals (95% CI) identified variables associated with early attrition. RESULTS: Of 139 faculty, 34% (95% CI = 26-42%) resigned within three years of hire. Attrition was associated with: perceived failure of the Department Chair to foster a climate of teaching, research, and service (OR = 6.03; 95% CI: 1.84, 19.69), inclusiveness, respect, and open communication (OR = 3.21; 95% CI: 1.04, 9.98). Lack of professional development of the faculty member (OR = 3.84; 95% CI: 1.25, 11.81); institutional recognition and support for excellence in teaching (OR = 2.96; 95% CI: 0.78, 11.19) and clinical care (OR = 3.87; 95% CI: 1.04, 14.41); and >50% of professional time devoted to patient care (OR = 3.93; 95% CI: 1.29, 11.93) predicted attrition. Gender, race, ethnicity, academic degree, department type and tenure status did not predict early attrition. Of still-active faculty, an additional 27 (48.2%, 95% CI: 35.8, 61.0) reported considering resignation within the 5 years. CONCLUSIONS: In this pilot study, one-third of new faculty resigned within 3 years of hire. Greater awareness of predictors of early attrition may help schools identify threats to faculty career satisfaction and retention.

Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.

INTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. METHODS: Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. RESULTS: Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. CONCLUSIONS: These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.

Cancer patient and survivor research from the cancer information service research consortium: a preview of three large randomized trials and initial lessons learned.

The authors describe 3 large randomized trials from the Cancer Information Service Research Consortium. Three web-based multimedia programs are being tested to help newly diagnosed prostate (Project 1) and breast cancer patients (Project 2) make informed treatment decisions and breast cancer patients prepare for life after treatment (Project 3). Project 3 also tests a telephone callback intervention delivered by a cancer information specialist. All participants receive standard print material specific to each project. Preliminary results from the 2-month follow-up interviews are reported for the initial wave of enrolled participants, most of whom were recruited from the Cancer Information Service (1-800-4-CANCER) telephone information program (Project 1: n =208; Project 2: n =340; Project 3: n =792). Self-reported use of the multimedia program was 51%, 52%, and 67% for Projects 1, 2, and 3, respectively. Self-reported use of the print materials (read all, most, or some) was 90%, 85%, and 83% for Projects 1, 2, and 3, respectively. The callback intervention was completed by 92% of Project 3 participants. Among those using the Cancer Information Service Research Consortium interventions, perceived usefulness and benefit was high, and more than 90% reported that they would recommend them to other cancer patients. The authors present 5 initial lessons learned that may help inform future cancer communications research.

The Living Well by Faith Health and wellness program for African Americans: an exemplar of community-based participatory research.

BACKGROUND: Using community-based participatory research (CBPR) as a guiding framework, a faith-based diet, nutrition and physical activity intervention for African Americans was implemented and evaluated as a small-scale randomized trial. METHODS: Five churches were recruited (intervention=3, control=2), resulting in an enrolled sample of 106 adults (intervention=74, control=32). The control group received a minimal intervention consisting of one educational workshop. The Living Well By Faith intervention group received a more intensive 8-week program. Classes were held twice a week and included educational workshops and exercise sessions. Both interventions were delivered at participating churches. Assessments for program evaluation occurred at baseline and 2-month follow-up. These included weight, blood pressure, percent body fat, and physical fitness using the step test. RESULTS: The sample was predominantly African American, female and well educated. At baseline, no significant differences between intervention and control groups were found for any of the primary endpoints. At 2-months follow up, the intervention group, compared to the control group, showed significant decreases in weight (P<.02), BMI (P<.05), and % body fat (P<.03), with a significant increase in physical fitness (P<.02). Systolic blood pressure also showed group differences in the predicted direction (P=.10). CONCLUSION: This study provides an exemplar of CBPR. The results obtained are sufficiently promising to support more research involving similar interventions of longer duration and with longer-term follow-up for evaluation.

Pharmacokinetics of single-dose intravenous ketorolac in infants aged 2-11 months.

BACKGROUND: Ketorolac is a parenterally available nonsteroidal antiinflammatory drug that nonselectively inhibits cyclooxygenase. Ketorolac is an attractive alternative to opioids in the pediatric population because of its favorable side effect profile; it provides postoperative analgesia similar to morphine, but is associated with significantly less respiratory depression, pruritus, and emesis. Despite the efficacy of ketorolac in young patients, there are minimal data to characterize the pharmacokinetic variables of ketorolac in infants younger than 6 months. METHODS: In this study, 17 infants younger than 1 year old, without renal or liver disease, undergoing elective surgery received a single-dose of IV ketorolac 0.5 mg/kg. Blood was sampled at 0, 5, 10, 15, 30, 60, and 120 minutes, and at 4, 6, 12, and 24 hours. Ketorolac levels were analyzed using a specific and validated high-performance liquid chromatography method with mass spectrometry (LC-LC/MS/MS). Pharmacokinetic analysis of individual subjects and population pharmacokinetic modeling was performed using SAAM II and PopKinetics, respectively (SAAM Institute, University of Washington). RESULTS: Characterization of pharmacokinetic parameters was possible in 14 subjects. The data were best described by a 2-compartment model. Estimated individual parameters were clearance 1.49 ± 1.12 mL/min/kg, Vss (volume of distribution at steady state) 0.31 ± 0.11 L/kg, and half-life of 236 ± 169 minutes. Estimated population pharmacokinetic parameters were clearance 1.52 mL/min/kg and Vss 0.29 L/kg. There was a trend toward lower clearances in younger patients. CONCLUSION: This is the first report of individualized pharmacokinetic parameters of ketorolac in children in which the majority of subjects were younger than 6 months old.

Intraoperative ventilation: incidence and risk factors for receiving large tidal volumes during general anesthesia.

BACKGROUND: There is a growing concern of the potential injurious role of ventilatory over-distention in patients without lung injury. No formal guidelines exist for intraoperative ventilation settings, but the use of tidal volumes (VT) under 10 mL/kg predicted body weight (PBW) has been recommended in healthy patients. We explored the incidence and risk factors for receiving large tidal volumes (VT > 10 mL/kg PBW). METHODS: We performed a cross-sectional analysis of our prospectively collected perioperative electronic database for current intraoperative ventilation practices and risk factors for receiving large tidal volumes (VT > 10 mL/kg PBW). We included all adults undergoing prolonged (≥ 4 h) elective abdominal surgery and collected demographic, preoperative (comorbidities), intraoperative (i.e. ventilatory settings, fluid administration) and postoperative (outcomes) information. We compared patients receiving exhaled tidal volumes > 10 mL/kg PBW with those that received 8-10 or < 8 mL/kg PBW with univariate and logistic regression analyses. RESULTS: Ventilatory settings were non-uniform in the 429 adults included in the analysis. 17.5% of all patients received VT > 10 mL/kg PBW. 34.0% of all obese patients (body mass index, BMI, ≥ 30), 51% of all patients with a height < 165 cm, and 34.6% of all female patients received VT > 10 mL/kg PBW. CONCLUSIONS: Ventilation with VT > 10 mL/kg PBW is still common, although poor correlation with PBW suggests it may be unintentional. BMI ≥ 30, female gender and height < 165 cm may predispose to receive large tidal volumes during general anesthesia. Further awareness of patients' height and PBW is needed to improve intraoperative ventilation practices. The impact on clinical outcome needs confirmation.

Postoperative delirium in the elderly: risk factors and outcomes.

OBJECTIVE: The purpose of this study was to describe the natural history, identify risk factors, and determine outcomes for the development of postoperative delirium in the elderly. BACKGROUND: Postoperative delirium is a common and deleterious complication in geriatric patients. METHODS: Subjects older than 50 years scheduled for an operation requiring a postoperative intensive care unit admission were recruited. After preoperative informed written consent, enrolled subjects had baseline cognitive and functional assessments. Postoperatively, subjects were assessed daily for delirium using the confusion assessment method-intensive care unit. Patients were also followed for outcomes. RESULTS: During the study period, 144 patients were enrolled before major abdominal (40%), thoracic (53%), or vascular (7%) operations. The overall incidence of delirium was 44% (64/144). The average time to onset of delirium was 2.1 +/- 0.9 days and the mean duration of delirium was 4.0 +/- 5.1 days. Several preoperative variables were associated with an increased risk of delirium including older age (P < 0.001), hypoalbuminemia (P < 0.001), impaired functional status (P < 0.001), pre-existing dementia (P < 0.001), and pre-existing comorbidities (P < 0.001). In a multivariable logistic regression model, pre-existing dementia remains the strongest risk factor for the development of postoperative delirium. Worse outcomes, including increased length of stay (P < 0.001), postdischarge institutionalization (P < 0.001), and 6 month mortality (P = 0.001), occurred in subjects who developed delirium. CONCLUSIONS: In the current study, delirium occurred in 44% of elderly patients after a major operation. Pre-existing cognitive dysfunction was the strongest predictor of the development of postoperative delirium. Outcomes, including an increased rate of 6 month mortality, were worse in patients who developed postoperative delirium.

Metabolic profiles in urine reflect nephrotoxicity of sirolimus and cyclosporine following rat kidney transplantation.

BACKGROUND: Cyclosporine and/or sirolimus impair recovery of renal transplants. This study examines the changes in urine metabolite profiles as surrogate markers of renal cell metabolism and function after cyclosporine and/or sirolimus treatment employing a rat kidney transplantation model. METHODS: Using inbred Lewis rats, kidneys were transplanted into bilaterally nephrectomized recipients followed by treatment with either CsA (cyclosporine) 10, Rapa (sirolimus) 1, CsA10/Rapa1 or CsA25/Rapa1 mg/kg/day for 7 days. On day 7, urine was analyzed by (1)H-NMR spectroscopy. Blood and kidney tissue drug concentrations, tissue high-energy compounds (including ATP, ADP) and oxidative stress markers (15-F(2t)-isoprostanes) in urine were measured by HPLC mass spectrometry. RESULTS: Changes in urine metabolites followed the order Rapa1 < CsA10 < CsA10/Rapa1 < CsA25/Rapa1. Compared with controls, CsA25/Rapa1 showed the greatest changes (creatinine -36%, succinate -57%, citrate -89%, alpha-ketoglutarate -75%, creatine +498%, trimethylamine +210% and taurine +370%). 15-F(2t)-isoprostane concentrations in urine increased in the combined immunosuppressant-treated animals ([CsA25/Rapa1]: 795 +/- 222, [CsA10/Rapa1]: 475 +/- 233 pg/mg/creatinine) as compared with controls (165 +/- 78 pg/mg creatinine). Rapa concentration in blood and tissues increased in the combined treatment (blood: 31 +/- 8 ng/ml, tissue: 1.3 +/- 0.4 ng/mg) as compared with monotherapy (blood: 14 +/- 8 ng/ml, tissue: 0.35 +/- 0.15 ng/mg). Drug blood concentrations correlated with isoprostane urine concentrations, which correlated negatively with citrate, alpha-ketoglutarate and creatinine concentrations in urine. Only CsA25/Rapa1 significantly reduced high-energy metabolite concentrations in transplant kidney tissue (ATP -55%, ADP -24%). CONCLUSION: Immunosuppressant drugs induce changes in urine metabolite patterns, suggesting that immunosuppressant-induced oxidative stress is an early event in the development of nephrotoxicity. Urine 15-F(2t)-isoprostane concentrations and metabolite profiles may be sensitive markers of immunosuppressant-induced nephrotoxicity.

Sacroiliac Joint Fusion Methodology - Minimally Invasive Compared to Screw-Type Surgeries: A Systematic Review and Meta-Analysis.

BACKGROUND: Sacroiliac (SI) joint fusion represents a unique area of orthopedic surgery with procedural literature dating to the early 1920s, showing limited innovation in either technique or hardware over the last 90 years. Recent improvements in the diagnosis and treatment of SI joint dysfunction warrant comparisons to older surgical techniques. OBJECTIVE: To evaluate treatment efficacies and patient outcomes associated with minimally invasive joint fusion in comparison to screw-type surgeries. STUDY DESIGN: Systematic review and meta-analysis. SETTING: Electronic databases, EMBASE, Pubmed (Medline), manual bibliography cross-referencing for published works until Dec. 31, 2017. METHODS: A thorough literature search was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Data repositories accessed included Pubmed and EMBASE, until Dec. 31, 2017. All studies evaluating sacroiliac joint fusion and reporting quantifiable outcome data were included. Exclusion criteria included nonhuman studies, qualitative reviews, and meta-analyses. Data compilation, coding, and extraction were performed using MedAware Systems proprietary software. Data from each study were extracted by 2 analysts, using software that allowed automatic comparisons of all data fields. The standardized mean difference (SMD) was used as a summary statistic for pooling outcomes data across studies. Multiple outcome measures were grouped into 3 categories, according to similarity of measurements - Pain, Disability/Physical Function, and Global/QOL. RESULTS: A total of 20 studies had adequate data to calculate a SMD, and were included in the meta-analysis. Results of iFuse trials were compared to screw type trials, pooled in 3 categories of outcomes - Pain, Disability/Physical Function, and Global/QOL. The Pain category showed a statistically significant (P = 0.03) difference in outcomes for patients receiving the iFuse implant compared to screw types (SMD = 2.04 [95%CI: 1.76 to 2.33] vs. 1.28 [95%CI: 0.47 to 2.09]), with iFuse showing significantly better outcomes. The Disability category also showed a statistically significant (P = 0.01) difference in outcomes for patients receiving the iFuse implant compared to screw types (SMD = 1.68 [95%CI: 1.43 to 1.94] vs. 0.26 [95%CI: -1.90 to 2.41]), with iFuse showing significantly better outcomes. For Global/Quality of Life (QOL) outcomes, there was a significant difference (P = 0.04) between iFuse and screw-type procedures (SMD = 0.99 [95%CI: 0.75 to 1.24] vs. 0.60 [95%CI: 0.33 to 0.88]), with iFuse showing significantly better outcomes. There was a statistically significant correlation between lower baseline Oswestry Disability Index (ODI) and Short Form 36 Health Survey (SF-36) values and better post treatment outcomes (r2 = 0.47, P < 0.01, and r2 = 0.30, P < 0.01, respectively). An association was found between pain at baseline and better outcomes (r2 = 0.21, P < 0.01), where worse baseline pain was associated with better outcomes. LIMITATIONS: There was a limited number of studies in this meta-analysis with treatments that could be properly classified as screw-type. CONCLUSION: In this analysis, compared to screw-type surgeries, the iFuse system showed statistically superior outcomes. This was the case when outcome measures were classified into 3 main categories - Pain, Disability/Physical Function, and Global/QOL. KEY WORDS: Meta-analysis, systematic review, sacroiliac joint, sacroiliac joint fusion.

The reno-vascular A2B adenosine receptor protects the kidney from ischemia.

BACKGROUND: Acute renal failure from ischemia significantly contributes to morbidity and mortality in clinical settings, and strategies to improve renal resistance to ischemia are urgently needed. Here, we identified a novel pathway of renal protection from ischemia using ischemic preconditioning (IP). METHODS AND FINDINGS: For this purpose, we utilized a recently developed model of renal ischemia and IP via a hanging weight system that allows repeated and atraumatic occlusion of the renal artery in mice, followed by measurements of specific parameters or renal functions. Studies in gene-targeted mice for each individual adenosine receptor (AR) confirmed renal protection by IP in A1(-/-), A2A(-/-), or A3AR(-/-) mice. In contrast, protection from ischemia was abolished in A2BAR(-/-) mice. This protection was associated with corresponding changes in tissue inflammation and nitric oxide production. In accordance, the A2BAR-antagonist PSB1115 blocked renal protection by IP, while treatment with the selective A2BAR-agonist BAY 60-6583 dramatically improved renal function and histology following ischemia alone. Using an A2BAR-reporter model, we found exclusive expression of A2BARs within the reno-vasculature. Studies using A2BAR bone-marrow chimera conferred kidney protection selectively to renal A2BARs. CONCLUSIONS: These results identify the A2BAR as a novel therapeutic target for providing potent protection from renal ischemia.

Chronic renal dysfunction following liver transplantation.

With most of the immunosuppressive protocols consisting of calcineurin inhibitors (CI), nephrotoxicity has become a major long-term complication often compromising outcome. In a single-center retrospective study, we reviewed 1173 liver transplantations to identify variables indicative for the occurrence of chronic renal dysfunction (CRD) (defined as > or = 1 episode of serum creatinine increase > or = 1.8 mg/dL > or = 2 wk). Chronic renal dysfunction was found in 137 (11.7%) of all transplants [82 (7%) early (after 3-12 months), 55 (4.7%) late-onset (> 12 months)]. Compared to 5-/10-yr survival rates in non-CRD transplants (84/74%) survival was significantly decreased in early (66/46%), but unchanged in late-onset CRD (98/86%). Rates of alcoholic cirrhosis and prior renal dysfunction were significantly increased in patients with CRD. In a multivariate logistic regression analysis, only cyclosporine A (CyA) as immunosuppression remained an independent risk factor. No correlations to age, gender, rejection/retransplantation or diabetes were found. Surprisingly, renal function (creatinine) showed no difference between patients on CI monotherapy (FK/CyA) compared to those who had mycophenolate mofetil (MMF) added. In liver transplantation, early onset CRD significantly compromises survival. CyA-based immunosuppression appears to have a stronger impact than FK. The fact that patients with long-term severe chronic renal dysfunction failed to improve under MMF rescue therapy emphasizes the importance of new diagnostic strategies to earlier identify at-risk patients.

Single-institution experience with pemetrexed and bevacizumab as salvage therapy in advanced non-small-cell lung cancer.

BACKGROUND: Second-line cytotoxic therapy for patients with advanced non-small-cell lung cancer (NSCLC) includes single-agent pemetrexed or docetaxel. The addition of bevacizumab to carboplatin/paclitaxel in the first-line setting was shown to improve survival and response. We assessed pemetrexed and bevacizumab compared with pemetrexed alone in the salvage setting. PATIENTS AND METHODS: Patients with advanced NSCLC, in whom at least first-line therapy failed and who received pemetrexed alone or pemetrexed/bevacizumab, were analyzed. RESULTS: From March 2005 through March 2006, we identified 25 patients treated with pemetrexed or pemetrexed/bevacizumab in the salvage setting. There were no significant differences in clinical features. All 25 were evaluable for overall survival, 21 for time to progression, and 19 for objective response evaluation. After a median follow-up of 9.3 months, there were no differences between the cohorts for median overall survival, time to progression, or objective disease control rate (partial response and stable disease). The 6-month survival rate was 56.3% for the pemetrexed group and 66.7% for the pemetrexed/bevacizumab group. There were no grade 3-5 hemorrhagic events. CONCLUSION: This retrospective single institution analysis showed that pemetrexed/bevacizumab was safely administered in the salvage setting of advanced NSCLC. Whether bevacizumab enhances the efficacy of pemetrexed remains to be determined and is the subject of an ongoing randomized clinical trial. Until those results are reported, off-label use of pemetrexed and bevacizumab is not recommended.

A survey of propofol abuse in academic anesthesia programs.

BACKGROUND: Although propofol has not traditionally been considered a drug of abuse, subanesthetic doses may have an abuse potential. We used this survey to assess prevalence and outcome of propofol abuse in academic anesthesiology programs. METHODS: E-mail surveys were sent to the 126 academic anesthesiology training programs in the United States. RESULTS: The survey response rate was 100%. One or more incidents of propofol abuse or diversion in the past 10 yr were reported by 18% of departments. The observed incidence of propofol abuse was 10 per 10,000 anesthesia providers per decade, a fivefold increase from previous surveys of propofol abuse (P = 0.005). Of the 25 reported individuals abusing propofol, 7 died as a result of the propofol abuse (28%), 6 of whom were residents. There was no established system to control or monitor propofol as is done with opioids at 71% of programs. There was an association between lack of control of propofol (e.g., pharmacy accounting) at the time of abuse and incidence of abuse at the program (P = 0.048). CONCLUSIONS: Propofol abuse in academic anesthesiology likely has increased over the last 10 yr. Much of the mortality is in residents. Most programs have no pharmacy accounting or control of propofol stocks. This may be of concern, given that all programs reporting deaths from propofol abuse were centers in which there was no pharmacy accounting for the drug.

Effect of intensive blood pressure control with valsartan on urinary albumin excretion in normotensive patients with type 2 diabetes.

BACKGROUND: Diabetes is the most common cause of renal failure in the United States, and data regarding the effects of aggressive blood pressure (BP) therapy in normotensive patients with type 2 diabetes are inadequate. METHODS: A total of 129 type 2 diabetic patients with a BP of <140/80 to 90 mm Hg without overt albuminuria were randomized to either intensive BP control (diastolic BP goal 75 mm Hg) using an angiotensin II receptor blocker, valsartan, versus moderate BP control (diastolic BP 80 to 90 mm Hg with placebo initially) to evaluate the effect on the change in urinary albumin excretion (UAE) from baseline. RESULTS: The mean entrance BP was 126 +/- 8.8/84 +/- 2.4 mm Hg. The mean follow-up period was 1.9 +/- 1.0 years. During the follow-up period, the mean BP was 118 +/- 10.9/75 +/- 5.7 for the intensive v 124 10.9/80 6.5 mm Hg for the moderate BP groups (P < .001). No difference was observed in change in creatinine clearance or serum creatinine from baseline between the two groups. An analysis of covariance model for change in log (UAE + 1), adjusting for age, HBA(1c), duration of diabetes, baseline log (UAE + 1), sex, and ethnicity resulted in a significant treatment difference at 2 years (P = .007) with intensive BP control reducing log (UAE+1) compared with moderate BP control. CONCLUSION: Intensive BP control with valsartan to <120/80 mm Hg in normotensive patients with type 2 diabetes and normo- or microalbuminuria significantly decreased the progression of UAE and in some cases caused regression of UAE.

Controlled endurance exercise training and VO2max changes in older adults: a meta-analysis.

This meta-analysis of controlled clinical trials quantifies the effect of aerobic exercise on VO2max (aerobic fitness) among sedentary older adults and examines the associations of such magnitude with variables of intervention. Forty-one trials including 2102 older subjects (within-group mean age of 60 years and older) were identified by searches of databases, hand searching, and cross-referencing. Outcomes were homogeneous. The pooled standardized effect size by a fixed-effect model showed a higher moderate effect (mean +/- SEM) of 0.64+/-0.05; 95% confidence interval, 0.56-0.73; p<0.001, representing a net increase in VO2max (mean +/- SEM) of 3.78+/-0.28 mL.kg-1.min-1; 95% confidence interval, 3.24-4.33; or a 16.3% improvement, compared with control groups. Greater improvement in VO2max was associated with training length more than 20 weeks and training intensity of approximately 60% but less than 70% of VO2max. Endurance training improves aerobic fitness in older adults, thus providing protective benefits for cardiovascular aging and quality of later life.